摘要
目的:利用生物信息学和网络药理学方法,对肿瘤基因组图谱(TCGA)数据库进行分析,探究豆甾醇与肺鳞癌(LUSC)发生发展相关的调控网络及药物作用机制。方法:综合TCGA RNA-seq数据,利用R 4.0.2进行加权基因共表达网络分析(WGCNA)、差异表达分析、基因本体论(GO)分析和蛋白相互作用网络(PPI)分析筛选核心基因,构建竞争性内源RNA(ceRNA)网络,基于网络药理学进行分子对接,分析豆甾醇作用于LUSC的机制。结果:WGCNA联合差异表达分析共确定801个信度高的基因,它们与染色体分离、有丝分裂核分裂、染色体着丝粒区域等功能密切相关。基于PPI分析得出前10个关键基因(CDC20、BUB1、CCNB2、BUB1B、CDK1、CCNB1、KIF2C、NDC80、CDCA8、CENPF),且均与生存率密切相关,最终构建了CDCA8与上游miRNA hsalet-7b-5p及与之关联的14个lncRNAs的ceRNA网络。豆甾醇与CDCA8对接良好。结论:14个lncRNAs与hsa-let-7b-5p竞争性调控CDCA8,可能在肺鳞癌发生发展过程中发挥重要作用,可能是豆甾醇干预LUSC的潜在机制。
OBJECTIVE:To mine the TCGA database and to identify regulatory network(s)which are related to lung squamous cell carcinoma(LUSC)and to drug actions.METHODS:Bioinformatics and network pharmacology methods were used on the following tasks:TCGA RNA-seq data,WGCNA analysis,differential expression analysis,GO analysis,PPI analysis and screening of core genes.Collected data were used to construct ceRNA network and molecular docking which were employed to analyze mechanisms of stigmasterol action on LUSC.RESULTS:A total of 801 genes with high reliability were identified by WGCNA combined with differential expression analysis.These genes were found to be involved with chromosome segregation,mitosis,chromosome centromere region,etc.Based on PPI analyses,the first 10 key genes(CDC20,BUB1,CCNB2,BUB1B,CDK1,CCNB1,KIF2C,NDC80,CDCA8,CENPF)were closely related to the survival rates.Finally,the ceRNA network of CDCA8 and its upstream miRNA hsa-let-7b-5p and associated 14 lncRNAs were constructed.Stigmasterol and CDCA8 docked well.CONCLUSION:Our data indicate that competitive regulation of CDCA8 by 14 lncRNAs and hsa-let-7b-5p played an important role in the occurrence and development of LUSC and that the mechanism involved stigmasterol intervention in LUSC.
作者
李经蕾
侯炜
LI Jinglei;HOU Wei(Guanganmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053;Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《癌变．畸变．突变》
CAS
2020年第6期423-429,共7页
Carcinogenesis,Teratogenesis & Mutagenesis
基金
北京市科学技术委员会计划资助项目(D161100005116001)。
关键词
肺鳞癌
加权基因共表达网络
竞争性内源RNA
分子对接
豆甾醇
lung squamous cell carcinoma
weighted gene coexpression network
ceRNA
molecular docking
stigmasterol
